Piezocatalytic removal of metronidazole (MET) using graphitic carbon nitride (g-C3N4, GCN)/sodium niobate (NaNbO3) heterojunction was investigated under ultrasonication. Herein, optimized GCN(50)/NaNbO3 heterojunction achieved 87.2% MET removal within 160 min (k = 0.0138 min−1). A new pathway for the generation of reactive oxygen species (ROS) via GCN(50)/NaNbO3 piezocatalytic heterojunction was identified. The type-II heterojunction formulated using optimized GCN(50)/NaNbO3 was found to generate hydroxyl radical (.OH); however, it was thermodynamically not feasible. The main reasons are; (i) piezopotential generated converted type-II to S-scheme heterojunction and resulted in the participation of high oxidizing potential holes in valence band (VB) of NaNbO3, and (ii) formation of depletion region at the GCN-water interface and subsequent improvement in the redox potential of holes, and (iii) piezopotential generated at NaNbO3 provided bias to GCN and established a piezo-electrocatalytic system. The higher screening of piezopotential in presence of external ions was found to reduce the generation of .OH. Overall, self-powered NaNbO3 has great ability to improve interfacial charge transfer at GCN(50)/NaNbO3 to form ROS.